Trial design

Following surgery, ∼2,000 patients (Pts) will have a Genomic Grade (GG) performed centrally on FFPE specimens by RT-PCR. Those with a high risk defined as high or equivocal GG will be randomized to HT alone vs CT + HT. Pts with a low GG will be followed as an observational cohort. OS (all deaths) is the primary endpoint. Secondary objectives include competing events, cost-effectiveness and Q-TWiST analysis, geriatric dimension, willingness and health-related quality of life including specific ELD15. Translational research will focus on prognostic biomarkers and pharmacogenetics. Sample size based on an expected 4-year OS benefit (87.5 vs 80%; HR 0.60), with bilateral test α = 0.05 and a statistical power of 80%. It will require to observe 129 events and to randomize 700 Pts over a planned duration of 4 years. As of March 2014, 65 centres in France and Belgium have included 890 Pts aged 70-92. Only 30 GG evaluations were not performed (consent withdrawal, 7; tumour blocks not available, 14; central pathology review discordance, 6; treatment choice, 3). In the main participating site, the study was not proposed to 20% of pre-screened Pts mostly because of team choice (50%) and inclusion criteria (25%). Amongst those informed, 66% accepted to participate.). Overall, of 860 cases with GG report, 346 (41%), 167 (19%) and 338 (39%) were low, equivocal and high GG respectively; 9 tests (1%) failed for technical reasons. The proportion of high risk tumours (high + equivocal GG, 59%) is similar to those observed in general BC populations (40% to 60%) and only 19 of high-risk cases were not randomized (consent withdrawal, 6, distant metastases, 3, treatment choice, 5, tumour phenotype not confirmed, 3, or laboratory values, 2). With 69% of target recruitment at mid-term of the planned inclusion period, we confirm the feasibility of such a multicentre program investigating the role of an innovative prognostic signature to better select adjuvant strategy in the elderly BC population.

Disclosure

H. Peyro Saint Paul: employee and stock holder QIAGEN. All other authors have declared no conflicts of interest.